Baruj Benacerraf, who has died aged 90, won the Nobel prize for his contribution to identifying the gene groups, called major histocompatibility complexes, that determine a person's susceptibility to certain diseases, as well as their capacity to mount an immune response and their compatibility for organ transplants. He shared the 1980 Nobel prize for medicine or physiology with two other immunologists whose work complemented his: together, their research has underpinned major advances in close compatibility between donor and recipient.

The first steps were taken by one of his fellow laureates, George Snell. Working in Maine, New England, in the 1940s, he recognised the existence of the major histocompatibility complex (MHC) and named it. He did this by inbreeding mice until they were so genetically similar that it was possible to transplant organs between them – demonstrating that compatibility was genetically determined and pinpointing the genes responsible. Then, in the 1950s, Jean Dausset in Paris identified the MHC in humans. Finally, in 1969, Benacerraf found that these MHC genes control the body's ability to respond to particular antigens. A few years later, he discovered, with colleagues, that the MHCs determine interactions between the immune system's T cells and B cells; furthermore, he found that both types of cell must carry the same MHC antigens for the individual to mount an effective immune response.

Benacerraf was born in Caracas, Venezuela, to Sephardic Jewish parents. His father, a textile importer, was from Spanish Morocco and his mother from French Algeria. The family moved to Paris when he was five and he received his schooling there; French language and culture was a major influence in his life. He was 19 when the second world war broke out, and his parents prudently returned to Caracas and their still-thriving business, which they expected him to join.

A year later they relocated to New York, where Benacerraf took a two-year degree that qualified him to enter medical school. Finding a place proved hard for a Jewish-French-Hispanic foreigner and he received endless rejections. Fortunately, he had impressed George Bakeman, a friend's father who was assistant to the president of the medical college in Richmond, Virginia. Benacerraf was accepted for one of the two remaining places there; of the 80 other students, two were Jewish and only one Hispanic. In 1943, he became a US citizen and married Annette Dreyfus, another Parisian Jewish refugee; she was the niece of the geneticist Jacques Monod, who would receive a 1965 Nobel prize for unravelling the way genes are transcribed.

Along with the rest of his class, Benacerraf was drafted into the army as part of the wartime medical training programme in 1943. He qualified in 1945, did a year's medical internship at Queens general hospital in New York and entered the US army medical corps. He was sent to Paris and Nancy where, joined by his wife, he practised community medicine for two years.

After his discharge in 1947, he decided on medical research, an unfashionable choice. Having been asthmatic since childhood, he was drawn to the study of allergy and hypersensitivity. Very little was then known about immunology: antibodies had been identified but their structure remained a mystery.

Entering this uncharted territory, he soon was "hooked for life as surely as if I had become addicted to heroin". In 1948, he took a training fellowship at Columbia University under Elvin Kabat, an immunochemist who taught him the value of intellectual rigour , experimental proof and accurate measurement. However, 18 months later, his father suffered a disabling stroke while living in Paris, and Benacerraf relocated there to wind down his business affairs. There he developed an inspiring research relationship with a young Italian, Guido Biozzi, with whom he studied the reticuloendothelial system – the cells that engulf bacteria and other particles – in relation to immunity.

Though Benacerraf had been delighted to go back to the land of his childhood, it gradually became clear that he was regarded as an outsider in France and his chances of establishing an independent laboratory were slender. So when the great doctor and biology essayist Lewis Thomas offered him a senior post at the New York university medical school with research support, he accepted. He stayed there from 1956 to 1961, working with many famous scientists. During this time he also managed a New York bank, the Colonial Trust Company, which he inherited from his father; he eventually retired from it so he could devote himself to science.

At this time he started the immunogenetics research that led to his Nobel prize. He was a professor of pathology in 1968 when he moved with some of his collaborators to the National Institute of Allergy and Infectious Diseases, in Mary- land, of which he was appointed head. Two years later, in 1970, and missing the climate of a university, he accepted the chair of pathology at Harvard medical school, and from 1980 was president of the Harvard-affiliated Dana-Farber cancer institute in Boston. There his banking experience helped him turn a budget deficit into a surplus.

Benacerraf wrote 300 research papers and books and honours were heaped on him worldwide. He retired in 1995, when he was 75, but remained on the board of Dana-Farber.

The transplantation immunologist Professor Leslie Brent said: "He was undoubtedly one of the important figures in the field of immunogenetics, and a great intellect." Barry Kay, emeritus professor of immunology at Imperial College London, said: "His seminal observation was that the body's responsiveness to foreign proteins [antigens] is controlled by the immune response genes he discovered. This led the way to tissue typing, transplantation immunology and an understanding, in general, of the genetic basis of the immune response." Some other experts felt that he was a bit of a smooth operator and that his colleagues in the discovery of the gene complex received insufficient recognition.

Benaceraff was inspiring to others and took pleasure from seeing his graduate students advance in their careers. Outside his work he was an avid reader, music lover and collected art.

His wife predeceased him by two months. He is survived by his daughter, Beryl, an obstetric radiologist, and Harvard medical school professor and his brother Paul, a philosophy professor at Princeton.

• Baruj Benacerraf, immunologist and geneticist, born 29 October 1920; died 2 August 2011